Epinephrine and norepinephrine are widely used to treat cardiovascular collapse during resuscitation with lipid emulsions in the treatment of drug toxicity including local or non-local anesthetics. The effect of the lipid emulsion Intralipid on the vasoconstriction induced by epinephrine or norepinephrine is, however, still unknown. In this study, the interaction of epinephrine and norepinephrine with the intravenous Intralipid emulsion was investigated by capillary electromigration techniques. Capillary electrokinetic chromatography was performed to determine the distribution coefficients by running the analytes under different experimental conditions (temperature, ionic strength, and pH) through a capillary filled with the background electrolyte containing Intralipid emulsion. In addition, the binding constants of the epinephrine and norepinephrine complexes with Intralipid emulsion were determined based on the effective electrophoretic mobility data obtained by electrokinetic chromatography at a wide concentration range of Intralipid emulsion. The obtained binding constants, as well as the distribution coefficients determined by electrokinetic chromatography, confirm that epinephrine and norepinephrine are hydrophilic compounds and that they are minimally distributed into the Intralipid emulsion. Therefore, their application as drugs for vasoconstriction upon Intralipid emulsion treatment is well motivated.

Department of Anesthesiology and Pain Medicine Gyeongsang National University College of Medicine Gyeongsang National University Hospital Jinju si Gyeongsangnam do Republic of Korea

Department of Chemistry University of Helsinki Helsinki Finland

Institute of Medical Science Gyeongsang National University Jinju si Gyeongsangnam do Republic of Korea

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Prague Czech Republic

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Weinberg G. L., VadeBoncouer T., Ramaraju G. A., Garcia‐Amaro M. F., and Cwik M. J., “Pretreatment or Resuscitation With a Lipid Infusion Shifts the Dose‐Response to Bupivacaine‐Induced Asystole in Rats,” Anesthesiology 88, no. 4 (1998): 1071–1075. PubMed

Xanthos T., Psichalakis N., Russell D., et al., “Intralipid™ Administration Attenuates the Hypotensive Effects of Acute Intravenous Amiodarone Overdose in a Swine Model,” American Journal of Emergency Medicine 34, no. 8 (2016): 1389–1393. PubMed

Harvey M. and Cave G., “Intralipid Outperforms Sodium Bicarbonate in a Rabbit Model of Clomipramine Toxicity,” Annals of Emergency Medicine 49, no. 2 (2007): 178–185. PubMed

Rosenblatt M. A., Abel M., Fischer G. W., Itzkovich C. J., and Eisenkraft J. B., “Successful Use of a 20% Lipid Emulsion to Resuscitate a Patient After a Presumed Bupivacaine‐Related Cardiac Arrest,” Anesthesiology 105, no. 1 (2006): 217–218. PubMed

Lee S. H. and Sohn J. T., “Mechanisms Underlying Lipid Emulsion Resuscitation for Drug Toxicity: A Narrative Review,” Korean Journal of Anesthesiology 76, no. 3 (2023): 171–182. PubMed PMC

Barker K., Stewart M., Rutter A., Whitfield P. D., and Megson I. L., “An In Vitro Study to Determine the Impact of Lipid Emulsion on Partitioning of a Broad Spectrum of Drugs Associated With Overdose,” BJA Open 10 (2024): 100292. PubMed PMC

Pugsley T. A, “Epinephrine and Norepinephrine,” in Kirk‐Othmer Encyclopedia of Chemical Technology, John Wiley & Sons, NY: 2001.

Szulczewski D. H. and Hong W.‐H., “Epinephrine,” in Analytical Profiles of Drug Substances, ed. Florey K. (Academic Press, 1978), 193–229.

Volpi A. and Toffoli F., “Therapeutic Dosage and Physicochemical Constants or Bases and Acids,” Bollettino Chimico Farmaceutico 118, no. 10 (1979): 594–609. PubMed

Parry W. H., Martorano F., and Cotton E. K., “Management of Life‐Threatening Asthma With Intravenous Isoproterenol Infusions,” American Journal of Diseases of Children 130, no. 1 (1976): 39–42. PubMed

Perrin D. D., Dissociation Constants of Organic Bases in Aqueous Solution (Butterworths, 1965).

De Queiroz Siqueira M., Chassard D., Musard H., et al., “Resuscitation With Lipid, Epinephrine, or Both in Levobupivacaine‐Induced Cardiac Toxicity in Newborn Piglets,” British Journal of Anaesthesia 112, no. 4 (2014): 729–734. PubMed

Mauch J., Martin Jurado O., Spielmann N., Bettschart‐Wolfensberger R., and Weiss M., “Resuscitation Strategies From Bupivacaine‐Induced Cardiac Arrest,” Pediatric Anesthesia 22, no. 2 (2012): 124–129. PubMed

Huang L., Ren Q., Yu S., Shao Y., Chen Y., and Huang X., “Supplement of Lipid Emulsion to Epinephrine Improves Resuscitation Outcomes of Asphyxia‐Induced Cardiac Arrest in Aged Rats,” Clinical Interventions in Aging 15 (2020): 1701–1716. PubMed PMC

Harvey M., Cave G., Prince G., and Lahner D, “Epinephrine Injection in Lipid‐Based Resuscitation From Bupivacaine‐Induced Cardiac Arrest: Transient Circulatory Return in Rabbits,” Anesthesia & Analgesia 111, no. 3 (2010): 791–796. PubMed

Karcioğlu M., Tuzcu K., Sefi̇l F., et al., “Efficacy of Resuscitation With Intralipid in a Levobupivacaine‐Induced Cardiac Arrest Model,” Turkish Journal of Medical Sciences 44 (2014): 330–336. PubMed

Fellows I. W., Bennett T., and Macdonald I. A., “The Metabolic and Cardiovascular Effects of Intravenous Infusion of Glucose or Intralipid in Normal Humans,” Clinical Nutrition 8, no. 3 (1989): 135–140. PubMed

French D., Smollin C., Ruan W., Wong A., Drasner K., and Wu A. H. B., “Partition Constant and Volume of Distribution as Predictors of Clinical Efficacy of Lipid Rescue for Toxicological Emergencies,” Clinical Toxicology 49, no. 9 (2011): 801–809. PubMed

Valko K. L., “Biomimetic Chromatography—A Novel Application of the Chromatographic Principles,” Analytical Science Advances 3, no. 3–4 (2022): 146–153. PubMed PMC

Jerga R., Brablecová V., Talášková V., et al., “A Novel Device for the Determination of Liposome/Water Partition Coefficients,” Talanta 269 (2024): 125434. PubMed

Laine J., Lokajova J., Parshintsev J., Holopainen J. M., and Wiedmer S. K., “Interaction of a Commercial Lipid Dispersion and Local Anesthetics in Human Plasma: Implications for Drug Trapping by “Lipid‐Sinks”,” Analytical and Bioanalytical Chemistry 396, no. 7 (2010): 2599–2607. PubMed

Muhonen J., Holopainen J. M., and Wiedmer S. K., “Interactions Between Local Anesthetics and Lipid Dispersions Studied With Liposome Electrokinetic Capillary Chromatography,” Journal of Chromatography A 1216, no. 15 (2009): 3392–3397. PubMed

Ravald H., Jaikishan S., Samuelsson J., et al., “Capillary Electrokinetic Chromatography for Studying Interactions Between Beta‐Blockers and Intralipid Emulsion,” Journal of Pharmaceutical and Biomedical Analysis 234 (2023): 115554. PubMed

Lishchuk V. and Wiedmer S. K., “Recent Trends in Capillary Electrokinetic Chromatography With Liposomes, Lipid Aggregates, and Lipid Emulsions,” Journal of Chromatography Open 6 (2024): 100163.

Owen R. L., Strasters J. K., and Breyer E. D., “Lipid Vesicles in Capillary Electrophoretic Techniques: Characterization of Structural Properties and Associated Membrane‐Molecule Interactions,” Electrophoresis 26, no. 4–5 (2005): 735–751. PubMed

Lokajová J., Railila A., King A. W. T., and Wiedmer S. K., “Determination of the Distribution Constants of Aromatic Compounds and Steroids in Biphasic Micellar Phosphonium Ionic Liquid/Aqueous Buffer Systems by Capillary Electrokinetic Chromatography,” Journal of Chromatography A 1308 (2013): 144–151. PubMed

Greenwood A. I., Tristram‐Nagle S., and Nagle J. F., “Partial Molecular Volumes of Lipids and Cholesterol,” Chemistry and Physics of Lipids 143, no. 1–2 (2006): 1–10. PubMed PMC

Lokajova J., Laine J., Puukilainen E., Ritala M., Holopainen J. M., and Wiedmer S. K., “Liposomes for Entrapping Local Anesthetics: A Liposome Electrokinetic Chromatographic Study,” Electrophoresis 31, no. 9 (2010): 1540–1549. PubMed

Harris D. C. and Lucy C. A., Quantitative Chemical Analysis (Macmillan Learning, 2020).

Šolínová V., Mikysková H., Kaiser M. M., Janeba Z., Holý A., and Kašička V., “Estimation of Apparent Binding Constant of Complexes of Selected Acyclic Nucleoside Phosphonates With β‐Cyclodextrin by Affinity Capillary Electrophoresis,” Electrophoresis 37, no. 2 (2016): 239–247. PubMed

Lee S. H., Park K.‐E., Eum K., et al., “Effect of Lipid Emulsion on Vasoconstriction Induced by Epinephrine or Norepinephrine in Isolated Rat Aorta,” Korean Journal of Anesthesiology 77, no. 5 (2024): 555–564. PubMed PMC

Hopkins E., Sanvictores T., and Sharma S, Physiology, Acid Base Balance (StatPearls; 2025). PubMed

Burger M. K. and Schaller D. J., Metabolic Acidosis (StatPearls, 2023). PubMed